Aerobic Exercise for Alzheimer's Disease

(BIMII Trial)

Overseen By Marc J Poulin, PhD, DPhil

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Dementia, Stroke, Terminal illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to uncover how aerobic exercise can improve brain health and slow cognitive decline in older adults at risk for Alzheimer's and related dementias. Participants will engage in a six-month supervised walk/jog program to determine if regular physical activity can boost cognitive performance. Ideal candidates are inactive individuals aged 50 to 80 with memory concerns and one or more vascular risk factors, such as high blood pressure or high cholesterol. The trial also seeks to understand the biological changes exercise causes that may benefit cognition. Findings could lead to exercise programs that help prevent dementia. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could shape future dementia prevention strategies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that aerobic exercise is safe for adults at increased risk for Alzheimer's disease and related dementias?

Research has shown that aerobic exercise, such as walking or jogging, is generally safe for most people, including those with Alzheimer's disease. Studies have found that these activities can improve fitness and might even help slow memory problems, especially when done regularly and following safety guidelines.

In one study, aerobic exercise prevented brain changes related to memory loss without causing serious side effects. Another study found that people with Alzheimer's who exercised had better heart and lung health, proving it to be a safe activity for them. Overall, these findings suggest that regular aerobic exercise is a safe way to boost brain health and may lower the risk of dementia. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for Alzheimer's, which often involve medication to manage symptoms or slow progression, aerobic exercise offers a non-pharmaceutical approach by potentially enhancing brain health through increased blood flow and improved cardiovascular fitness. Researchers are excited because aerobic exercise can increase the brain's plasticity, which might help maintain memory and cognitive function. Additionally, this approach encourages physical activity, which can have various health benefits beyond cognitive improvement, making it a holistic option for managing Alzheimer's symptoms.

What evidence suggests that aerobic exercise is effective for Alzheimer's disease?

Studies have shown that aerobic exercise, which participants in this trial may receive, can greatly improve thinking skills and quality of life for people with Alzheimer's disease. For example, research indicates that regular aerobic exercise can help prevent the shrinking of the hippocampus, a part of the brain important for memory. This type of exercise also reduces symptoms like memory loss and confusion. Other studies have found that aerobic exercise helps with daily activities and reduces mood and behavior-related issues. Overall, evidence suggests that aerobic exercise is a promising way to support brain health in those at risk for Alzheimer's and related conditions. Meanwhile, participants in the control group of this trial will engage in Stretch and Strength sessions, which prior research suggests are ineffective or minimally effective. ^{6 7 8 9 10}

Who Is on the Research Team?

Marc J Poulin, PhD, DPhil

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for inactive adults aged 50-80 with memory complaints but no dementia, and at least one vascular risk factor like high blood pressure or diabetes. They should not be doing vigorous exercise more than twice a week and must speak English fluently. People with serious illnesses, history of stroke, or other conditions that could affect the study can't join.

Inclusion Criteria

I am between 50-80 years old, feel I have memory issues, but don't have dementia, and have risk factors for Alzheimer's or related diseases.

I have a history of high blood pressure, diabetes, obesity (BMI <40), high cholesterol, smoking, or past heart disease without recent symptoms.

Subjective cognitive symptoms self-reported using the MAC-Q Memory Complaint Questionnaire with a score of ≥25

Exclusion Criteria

History of dementia

I am not fluent in English.

Contraindication for the intervention

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 6-month aerobic exercise intervention, including supervised sessions 3 days/week with progressive intensity and duration.

6 months

3 visits per week (in-person)

Follow-up

Participants are monitored for changes in cognition, cerebral blood flow, and cerebrovascular reserve, with assessments at 12 and 18 months post-intervention.

12 months

Assessments at 12 and 18 months

What Are the Treatments Tested in This Trial?

Interventions

• Aerobic exercise
• Stretch and Strength

Trial Overview The trial tests if regular aerobic exercise can prevent or slow down cognitive decline in older adults at risk of Alzheimer's Disease and related dementias (ADRD). Participants will do either aerobic exercises or stretching-toning exercises to see which helps brain health and cognition more.

How Is the Trial Designed?

Group I: Stretch and Strength Experimental Treatment 1 Intervention

A control group will meet on a similar schedule as the exercise group for sessions on stretching and toning but without aerobic exercise. Based on prior RCTs of similar interventions the investigators expect this control to be ineffective or minimally effective, but anticipate that it will increase participant enthusiasm and retention. All assessments will be conducted in this arm.

Group II: Aerobic exercise Experimental Treatment 1 Intervention

Participants will take part in a supervised 6-month-long aerobic (walk/jog) training program held 3 days/week. Each session will include a 5-min warm-up, 20-40 min of aerobic exercise (walking, jogging), 5-min cool-down, and stretching. Exercise prescriptions will follow current principles and guidelines established by ACSM/AHA, including sufficient warm-up, cool-down, and ongoing provision of safety precautions/exercise tips. As participants progress, the duration of aerobic exercise will increase from 20 (month 1) to 30 (months 2-3) and 40 min (months 4-6), with proportional increases to warm-up and cool-down periods. Exercise intensity will be based on individual maximal oxygen uptake (VO2 max), measured at baseline. Intensity will build from 30-45% (months 1-3) to mitigate the risk of injury and will progress to 60-70% (months 4-6) heart rate reserve (HRR).

Aerobic exercise is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Aerobic Exercise for:

• Rehabilitation after stroke
• Improvement of physical function
• Enhancement of cognitive function
• Reduction of depression

Approved in European Union as Aerobic Exercise for:

• Cardiovascular rehabilitation
• Improvement of physical function
• Enhancement of cognitive function

Approved in Canada as Aerobic Exercise for:

• Rehabilitation after stroke
• Improvement of physical function
• Enhancement of cognitive function

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

A 26-week supervised aerobic exercise program improved functional ability in individuals with early Alzheimer's disease, as evidenced by a significant gain in scores on the Disability Assessment for Dementia.

Increased cardiorespiratory fitness from the exercise was linked to better memory performance and less hippocampal atrophy, indicating that improving physical fitness may help support brain health in early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial. Morris, JK., Vidoni, ED., Johnson, DK., et al.[2023]

Aerobic exercise training may improve physical fitness, performance, daily living activities, cognition, and psychological symptoms in older adults with Alzheimer's disease, based on a review of 12 studies.

The Functional Impact of aerobic exercise Training in Alzheimer's disease (FIT-AD) model was developed to guide future research and practice, emphasizing the interconnected benefits of aerobic exercise for individuals with Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guiding research and practice: a conceptual model for aerobic exercise training in Alzheimer's disease. Fang Yu, .[2021]

A 2-month aerobic training program showed that older men with moderate Alzheimer's disease (AD) can improve their cardiorespiratory fitness, while those with severe AD may not benefit as much, indicating variability in response to exercise.

The study suggests that a longer duration of aerobic training, such as 6 months, may be more effective for improving fitness in older adults with AD, highlighting the need for tailored exercise programs based on individual fitness levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic training for older men with Alzheimer's disease: individual examples of progression. Yu, F., Leon, AS., Bliss, D., et al.[2021]

A 6-month moderate intensity cycling program improved cardiorespiratory fitness in 8 participants with Alzheimer's disease, as indicated by a significant reduction in heart rate during exercise tests.

However, the study did not find significant changes in lower extremity function or overall physical performance, suggesting that while aerobic exercise can enhance fitness, its effects on physical functioning may need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintaining physical fitness and function in Alzheimer's disease: a pilot study. Yu, F., Savik, K., Wyman, JF., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11631704/

A meta-analysis of the efficacy of physical exercise ... The results showed that physical exercise might significantly improve ADL in Alzheimer's patients (SMD = 0.33, 95% CI: 0.12–0.54, I2 = 81.7%).

2. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724002693

Effectiveness of Physical Exercise on Alzheimer's disease. ... This review found moderate evidence of the positive impact that aerobic physical exercise could have in reducing neuropsychiatric symptoms and improving ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11752035/

Effects of aerobic exercise on cognitive function and quality ... The study revealed that aerobic exercise was conducive to the improvement of cognitive function and quality of life among patients with AD.

4. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1243869/full

Exercise therapy to prevent and treat Alzheimer's disease Aerobic exercise (with an intensity of 50–75% of VO2 max) prevents hippocampal volume reduction, spatial memory reduction, and learning reduction.

5. bmcgeriatr.biomedcentral.com bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-024-05060-8

Effective dosage and mode of exercise for enhancing ... Our study not only corroborates previous findings on the efficacy of aerobic exercise in enhancing cognitive function in AD patients but also ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10436316/

Exercise therapy to prevent and treat Alzheimer's disease - PMC Aerobic exercise (with an intensity of 50–75% of VO2 max) prevents hippocampal volume reduction, spatial memory reduction, and learning reduction.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01128361

Pilot Study of Aerobic Exercise in Early Alzheimer's ... The current study will provide data to estimate expected effect sizes for power analyses and sample size calculations. It will also provide an opportunity to ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1041610224033994

The effectiveness of physical exercise interventions in ... There is clear evidence that physical activity and especially aerobic exercise may be effective in the management of NPS.

9. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2016.05.004

Effect of aerobic exercise on physical performance in patients ... Aerobic exercise is feasible in home-dwelling patients with Alzheimer's disease (AD) · Aerobic exercise improves cardiorespiratory fitness in ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3258000/

Physical Exercise as a Preventive or Disease-Modifying ... CONCLUSION. These data suggest that aerobic exercise is associated with a reduced risk of cognitive impairment and dementia; it may slow dementing illness. A ...